SP8: Charting motor network connectivity and plasticity in genetically determined dystonia syndromes
Principle Investigator: Alexander Münchau
Co-Investigator: Andrea Kühn
Co-Leader: Tobias Bäumer
Dystonia is a disorder of deficient inhibition and abnormal plasticity in different brain circuits engaged in motor control, particularly the primary motor cortex (M1), dorsal premotor (PMd)-M1 networks, basal-ganglia-thalamo-cortical (BGTC) loops, cerebello-thalamo-cortical (CTC) projections.
Although evidence in increasing that intrinsic M1 / BGTC circuits, PMd-M1 and CTC pathways are pathologically active in dystonia the interplay of such aberrant activity in different networks and the relation to the underlying genotype are undetermined. Genotype may be a stronger determinant of motor system alterations than phenotype. In this project, we will explore the connectivity, activity and plasticity in M1/ BGTC, PMd-M1 and CTC projections in asymptomatic and symptomatic DYT1-, DYT 6- and GNAL-mutation carries using combined transcranial magnetic stimulation (TMS), diffusion tensor imaging (DTI), eyeblink classical conditioning, repetitive TMS (rTMS) and pallidal deep brain stimulation (DBS).
Correlations between TMS and DTI will be made employing tract-based spatial statistics. We expect genotype specific network abnormalities that could represent a rationale to individually tailor brain stimulation depending on motor pathway alterations.
The objectives are:
To characterize intracortical, premotor-motor, basal-ganglia-thalamo-cortical and cerebello-thalamo-cortical networks in genetically determined DYT1-, DYT6 and GNAL associated dystonia with the aim to delineate endophenotypes at a system level, which represents a prerequisite for further genetic analyses and offers the perspective of individualised treatment.